POS0177 INFECTION INCIDENCE, TIMING, AND DOSE DEPENDENCY IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH RITUXIMAB: A RETROSPECTIVE COHORT STUDY
Authors: L. Veeken, M. Opdam, L. M. Verhoef, C. Popa, R. Van Crevel, A. Den Broeder
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Rituximab (RTX) is a safe and effective treatment for rheumatoid arthritis (RA). In The Netherlands, RTX is usually administered intravenously every six months in standard low dose (2x500 mg or 1x1000 mg). Ultra-low doses (1x500 or 1x200 mg every six months) have shown to be effective as well for continued treatment for RA patients who are in remission.<sup>[1]</sup> Despite its efficacy and safety, there are some concerns about infection risk for RTX. Preliminary data suggest a dose and time dependent infection risk with a higher risk in higher doses and shortly after infusion.<sup>[1,2]</sup> <h3>Objectives</h3> The aim of this study was to compare infection incidence rates (IRs) in a real-life population of RA patients between standard low or ultra-low dosed RTX, with an additional focus on time since last infusion. <h3>Methods</h3> RA patients treated with standard low or ultra-low dosed RTX in the Sint Maartenskliniek (The Netherlands) between 2012 and 2021 were included in this retrospective cohort study. Patient-, disease-, treatment- and infection characteristics were retrieved from electronic health records. Infusions given within 30 days were considered as one RTX treatment. As RTX is usually given every six months, only infections occurring within 6 months after administration were included. In absence of the exact date of an infection, the start date was imputed using single imputation based on the known start week, month or period of infection. Infection IRs, dose-dependency and time relations with RTX infusion were analyzed using mixed-effects Poisson regression with correction for confounders. After Bonferroni correction, results were considered statistically significant if p&lt;0.025. <h3>Results</h3> Among 490 patients followed for 1254 patient years, 819 infections were identified (65/100 patient years). Most infections were mild (89%) and respiratory tract infections were most prevalent (49%). Infection IRs were 41, 54 and 71 per 100 patient years for doses of 200 mg, 500 mg and 1000 mg, respectively. Incidence rate ratio (IRR) was significantly lower only for 200 mg in comparison to 1000 mg (adjusted IRR 0.64 (95% CI 0.45-0.93, p=0.019)). Infections seemed to occur more frequently – although not statistically significant - within the first two months after infusion in comparison to later on in the treatment cycle (table 1). <h3>Conclusion</h3> Ultra-low dosing, and especially 200 mg, of RTX is associated with a lower infection risk in RA. Additionally, a trend of higher IR of infections shortly after infusion was found. Therefore, future optimization focusing on ultra-low dosing and slow release of RTX (e.g. by subcutaneous administration) may further lower infection risk in addition to reducing costs and administration time. In clinical practice, physicians should consider offering 500 mg and especially 200 mg RTX dosage to RA patients in sustained remission, instead of continuing the 1000mg dosage. <h3>References</h3> [1]Verhoef LM, den Broeder N, Thurlings RM, et al. Ultra-low doses of RTX for continued treatment of rheumatoid arthritis (REDO study): a randomised controlled non-inferiority trial. Lancet Rheumatol. 2019; 1: e145-e153. [2]Opdam MAA, de Leijer JH, den Broeder N, et al. Rituximab dose-dependent infection risk in rheumatoid arthritis is not mediated through circulating immunoglobulins, neutrophils or B cells. Rheumatology (Oxford). 2022;62(1):330-334. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Lara Veeken: None declared, Merel Opdam: None declared, L.M. Verhoef: None declared, Calin Popa: None declared, Reinout van Crevel: None declared, Alfons den Broeder Grant/research support from: Grants for quality of care projects and research on RA, PsA and axSpA from Abbvie, Galapagos, Pfizer, Novartis, Lilly, Sanofi, Gilead to the institution/department rheumatology.